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Biomedical subjects

R G Cooke

Publications and source records attributed to R G Cooke.

At least 73 records · Page 4Linked to original sources

Loss of biological and immunological activity of oxytocin from goat plasma on storage.

Storage of plasma at -30 degrees C, with no prior treatment, resulted in significant (P less than 0.01) reductions in the biological and immunological activities of oxytocin after 10 days and further reductions after 20 days. Acidification with 0.1 N hydrochloric acid, or snap-freezing in solid carbon dioxide-acetone, before storage afforded some protection against these losses and a combination of both treatments preserved the biological and immunological activities for 20 days despite thawing and refreezing after 10 days.

Animals↗

Plasma concentrations of testosterone and 5 alpha-dihydrotestosterone around luteolysis in goats and their behavioural effects after ovariectomy.

In non-pregnant goats, increased peripheral plasma concentrations of testosterone and 5 alpha-dihydrotestosterone (DHT) occurred at the start of luteal regression and before the day of oestrus. Intramuscular injections of testosterone (10 mg) in arachis oil to progesterone-primed ovariectomized goats induced oestrous behaviour; similar injections of DHT failed to do so. It is suggested that conversion of testosterone to oestrogens by aromatization induces oestrous behaviour in the goat while reduction of testosterone to DHT does not.

Animals↗

The nonlinear kinetics of desipramine and 2-hydroxydesipramine in plasma.

Plasma levels of desipramine (DMI) and the unconjugated form of its principal metabolite 2-hydroxydesipramine (OH-D) were measured under steady-state conditions in nine depressed inpatients during treatment with 75 mg DMI every 12 hr and after at least 1 wk of an increased dose of DMI (after steady state). When DMI dosage was raised after an initial steady state had been reached, the rise in plasma DMI level was proportionately greater than the increase in dosage, suggesting saturation of DMI elimination pathways. Levels of OH-D rose in proportion to dose, suggesting saturation of DMI elimination by 2-hydroxylation could not explain DMI plasma level changes. In contrast, there were no dose-dependent effects on the disposition of amitriptyline or its metabolite nortriptyline in subjects receiving the same amitriptyline dose.

Administration, Oral↗

Biological half-life of oxytocin in the goat.

The disappearance of oxytocin from the peripheral circulation of the goat after a single intravenous injection followed a biexponential curve. The mean (+/- SD) half-life, calculated from the slower component of this decline, was 22.3 +/- 0.6 minutes. The volume of the central compartment was about twice the volume of the vascular compartment and the total apparent volume of distribution was more than twice the size of the extracellular compartment.

Animals↗

Delayed luteolysis and suppression of the pulsatile release of oxytocin after indomethacin treatment in the goat.

Luteolysis in the goat was characterised by the pulsatile appearance of both oxytocin and 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM), the primary pulmonary metabolite of prostaglandin (PG) F2 alpha, in the peripheral circulation. The episodic, surge release of oxytocin was superimposed on declining levels which paralleled the fall in progesterone concentrations. Daily subcutaneous administration of the prostaglandin synthetase inhibitor indomethacin (10 mg kg-1) between days 11 and 16, delayed luteolysis and suppressed both the decline in oxytocin concentrations and the pulsatile appearance of both oxytocin and PGFM in the peripheral circulation. Although there was little evidence of the release of the two hormones being synchronised, the results suggest that PGF2 alpha may stimulate pulsatile oxytocin release at luteolysis.

Animals↗

Suppression of pulsatile release of oxytocin during early pregnancy in the goat.

Concentrations of oxytocin were measured in the peripheral plasma of four goats during both luteolysis in the oestrous cycle and the early stages of pregnancy. The two profiles were similar, each showing a decrease from day 12 onwards; during luteolysis, however, in the non-pregnant goats this decline was characterized by frequent pulses of oxytocin in excess of 40 pg/ml; these were absent during the corresponding period of pregnancy. It is suggested that the embryo may prevent luteal regression in pregnancy by suppressing pulsatile release of oxytocin, which may be responsible for the release of prostaglandin F2 alpha from the uterus.

Animals↗

Prevention of the luteolytic action of oxytocin in the goat by inhibition of prostaglandin synthesis.

Oxytocin-induced luteolysis in goats was associated with significant increases in peripheral plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F2alpha (PGFM). Oral administration of the prostaglandin (PG) synthetase inhibitor meclofenamic acid (l g/day) prevented both the luteolytic action of oxytocin and the increase in PGFM concentrations. These results confirm that the luteolytic effect of oxytocin is mediated via the production and release of PGF2alpha.

Journal Article↗

Peripheral plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F2 alpha and progesterone around luteolysis and during early pregnancy in the goat.

Peripheral plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) and progesterone were determined during both luteolysis in the oestrous cycle and early pregnancy in four goats. Luteal regression, characterised by decreasing progesterone concentrations, began on day 12 or 13. PGFM concentrations showed a pulsatile pattern around this time, with peak concentrations increasing markedly as progesterone levels fell and oestrus approached. During early pregnancy progesterone concentrations did not fall after day 12 and no marked elevation of PGFM above basal values of 50-150 pg/ml was detected.

Animals↗

Plasma concentrations of 13, 14-dihydro-15-keto prostaglandin F(2alpha) and progesterone during oxytocin-induced oestrus in the goat.

Fertile oestrus was induced in dairy goats by sub-cutaneous administration of 100 i.u. oxytocin per day between days 3-6 of the oestrous cycle. Peripheral plasma concentrations of 13, 14-dihydro-15-keto-prostaglandin F(2alpha) (PGFM), the major metabolite of prostaglandin (PG) F(2alpha), were elevated significantly (P<0.001), relative to controls, 30 minutes after oxytocin with peak values of between 300-800 pg ml(-1). Unlike control animals, plasma progesterone concentrations did not rise in the oxytocin-treated group after day 4. These results lend support to the hypothesis that the luteolytic effect of oxytocin in goats may be mediated via uterine PG production.

Journal Article↗

Anti-convulsant activity of diazepam and clonidine on metaldehyde-induced seizures in mice: effects on brain gamma-amino butyric acid concentrations and monoamine oxidase activity.

Metaldehyde when administered orally to mice at a dose of 1 g kg-1 produced convulsions and death within 2 h. Brain concentrations of gamma-aminobutyric acid (GABA) were significantly reduced and monoamine oxidase (MAO) activity significantly increased in these animals relative to controls. Treatment with either intraperitoneal diazepam or clonidine 20 min after administration of metaldehyde delayed the onset of toxic symptoms and reduced the mortality rate. In those mice which survived longer than 5 h, brain concentrations of GABA, though still not restored to control values, were significantly higher than those in the mice which died. Clonidine, unlike diazepam, also inhibited the increase in brain MAO activity.

Acetaldehyde↗

Pharmacological aspects of metaldehyde poisoning in mice.

Metaldehyde, when administered orally to mice at a dose of 1 g kg-1, produced convulsions and death within 2 h. Brain concentrations of noradrenaline (NA) 5-hydroxytryptamie (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were significantly reduced in these animals relative to controls. Treatment with either intraperitoneal clonidine or diazepam 20 min after administration of metaldehyde reduced the mortality rate and in mice surviving for 5 h, the decrease in brain NA and 5-HT concentrations were significantly reduced.

Acetaldehyde↗

Oxytocin-induced oestrus in the goat.

Subcutaneous administration of oxytocin between days 3-6, inclusive, significantly reduced the length of the oestrous cycle in goats. Concomitant oral administration of the prostaglandin synthetase inhibitor, meclofenamic acid, completely prevented this effect. Oxytocin treatment did not affect the duration of the posttreatment cycles.

Journal Article↗

Bioavailability of oxytetracycline dihydrate tablets in dogs.

Plasma oxytetracycline concentrations were studied in four healthy beagles after oral administration of four different commercial preparations of oxytetracycline dihydrate tablets. Although no statistically significant differences were found in the biological availability between the four tablets, assessed by the peak plasma level and the area under the plasma concentration--time curve, there was great variation in the plasma concentrations of oxytetracycline achieved in the sixteen experiments. This variation was not related to the in vitro dissolution properties of the tablets. As the amount of oxytetracycline dihydrate administered in the experiments was almost the maximum recommended dose and the mean peak plasma concentrations were either below or at the lower end of the therapeutic concentration range, it is suggested that higher oral doses than those officially recommended are required to attain effective plasma levels.

Animals↗